Publication Title: 
American Journal of Pharmacogenomics: Genomics-Related Research in Drug Development and Clinical Practice

No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms.

Abdolmaleky, Hamid M.
Thiagalingam, Sam
Wilcox, Marsha
Publication Title: 
Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion

The dopamine D4 receptor (DRD4) is the most important gene in psychiatric genetics since its involvement in the physiology of behavior, pharmacology response and psychopathology. DRD4's sequence gene present some polymorphism such as in the exon 3 constituted from 2 to 10 copies of repetitive sequences of 48 base pair (bp), from class variable number tandem repeats (VNTR). An additional genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the variation -521 C by T of the promoter region.

Aguirre-Samudio, Ana Julia
Nicolini, Humberto
Publication Title: 
Journal of Neurochemistry

Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails.

Stadler, Florian
Kolb, Gabriele
Rubusch, Lothar
Baker, Stephen P.
Jones, Edward G.
Akbarian, Schahram
Publication Title: 
Molecular Psychiatry

Genetic studies implicating the region of human chromosome 18p11.2 in susceptibility to bipolar disorder and schizophrenia have observed parent-of-origin effects that may be explained by genomic imprinting. We have identified a transcriptional variant of the GNAL gene in this region, employing an alternative first exon that is 5' to the originally identified start site. This alternative GNAL transcript encodes a longer functional variant of the stimulatory G-protein alpha subunit, Golf.

Corradi, J. P.
Ravyn, V.
Robbins, A. K.
Hagan, K. W.
Peters, M. F.
Bostwick, R.
Buono, R. J.
Berrettini, W. H.
Furlong, S. T.
Publication Title: 
Archives of General Psychiatry

BACKGROUND: Schizophrenia is frequently accompanied by hypometabolism and altered gene expression in the prefrontal cortex. Cellular metabolism regulates chromatin structure, including covalent histone modifications, which are epigenetic regulators of gene expression. OBJECTIVE: To test the hypothesis that down-regulated metabolic gene expression is associated with histone modification changes in the prefrontal cortex of subjects with schizophrenia.

Akbarian, Schahram
Ruehl, Martin G.
Bliven, Erin
Luiz, Lori A.
Peranelli, Amy C.
Baker, Stephen P.
Roberts, Rosalinda C.
Bunney, William E.
Conley, Robert C.
Jones, Edward G.
Tamminga, Carol A.
Guo, Yin
Publication Title: 
Neuroscience and Biobehavioral Reviews

In mammals the neonatal period is a time of significant social interaction. This is true even in solitary species as females spend a significant amount of time nursing and caring for their offspring. In social species interactions may also include the father, older siblings and extended family members. This period is a time of significant development, including organization of the central nervous system, and therefore a time when the degree and type of social interaction influences the development and expression of social behavior in adulthood.

Cushing, Bruce S.
Kramer, Kristin M.
Publication Title: 
Medical Hypotheses

Molecular data and gene expression data and recently mitochondrial genes and possible epigenetic regulation by non-coding genes is revolutionizing our views on schizophrenia. Genes and epigenetic mechanisms are triggered by cell-cell interaction and by external stimuli. A number of recent clinical and molecular observations indicate that epigenetic factors may be operational in the origin of the illness.

Gonz·lez-Hern·ndez, J. A.
Pita-Alcorta, C.
CedeÒo, I. R.
Publication Title: 
Genes, Brain, and Behavior

The results of a large body of candidate gene studies of behavioural and psychiatric phenotypes have been largely inconclusive, with most findings failing to replicate reliably.

MunafÚ, M. R.
Publication Title: 
Journal of Neural Transmission (Vienna, Austria: 1996)

DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA methylation processes. Recently, it has been shown that the genomic DNA methylation in patients with alcoholism is increased. In the present controlled study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT-3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66): DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2) expression.

Bˆnsch, D.
Lenz, B.
Fiszer, R.
Frieling, H.
Kornhuber, J.
Bleich, S.
Publication Title: 
Journal of Child Psychology and Psychiatry, and Allied Disciplines

Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene-environment correlations.

Rutter, Michael
Moffitt, Terrie E.
Caspi, Avshalom


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